rs3816465

Positions:

• chr7-158735911-A-G
• chr7-158735911-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367773.1(ESYT2):​c.2400-303T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 151,984 control chromosomes in the GnomAD database, including 39,300 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.71 (39300 hom., cov: 31)
• Consequence: ESYT2 NM_001367773.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

Genes affected

ESYT2 (HGNC:22211): (extended synaptotagmin 2) Enables calcium ion binding activity; identical protein binding activity; and phospholipid binding activity. Predicted to be involved in endocytosis; endoplasmic reticulum-plasma membrane tethering; and lipid transport. Located in endoplasmic reticulum-plasma membrane contact site. Is extrinsic component of cytoplasmic side of plasma membrane; integral component of plasma membrane; and intrinsic component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESYT2	NM_001367773.1	c.2400-303T>C		intron_variant		ENST00000275418.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESYT2	ENST00000275418.13	c.2400-303T>C		intron_variant		5	NM_001367773.1
ESYT2	ENST00000251527.10	c.2337-303T>C		intron_variant		1		P2
ESYT2	ENST00000652148.1	c.2481-303T>C		intron_variant				A2
ESYT2	ENST00000435514.3	n.1295-303T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107813 AN: 151866 Hom.: 39293 Cov.: 31

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.924

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.728

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.710 AC: 107874 AN: 151984 Hom.: 39300 Cov.: 31 AF XY: 0.707 AC XY: 52465 AN XY: 74252

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.757

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.782

Gnomad4 NFE AF: 0.789

Gnomad4 OTH AF: 0.725

Alfa AF: 0.755 Hom.: 18880

Bravo AF: 0.700

Asia WGS AF: 0.510 AC: 1777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.55
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3816465; hg19: chr7-158528602;